Trial Evaluating the Efficacy and Safety of Oral Vadadustat Once Daily (QD) and Three Times Weekly (TIW) for the Maintenance Treatment of Anemia in Hemodialysis Subjects Converting From Erythropoiesis-Stimulating Agents (ESAs)
Phase 3b, Randomized, Open-label, Active-controlled Trial Evaluating the Efficacy and Safety of Oral Vadadustat Once Daily (QD) and Three Times Weekly (TIW) for the Maintenance Treatment of Anemia in Hemodialysis Subjects Converting From Erythropoiesis-Stimulating Agents (ESAs)
3 other identifiers
interventional
319
6 countries
59
Brief Summary
This trial will be conducted to demonstrate the efficacy and safety of vadadustat compared to darbepoetin alfa for the maintenance treatment of anemia in hemodialysis participants after conversion from current erythropoiesis-stimulating agent (ESA) therapy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started May 2020
59 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 16, 2020
CompletedFirst Posted
Study publicly available on registry
March 18, 2020
CompletedStudy Start
First participant enrolled
May 27, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 26, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
June 22, 2022
CompletedResults Posted
Study results publicly available
May 22, 2025
CompletedMay 22, 2025
May 1, 2025
1.5 years
March 16, 2020
September 3, 2024
May 7, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change From Baseline in Hb to the Average Over the Primary Evaluation Period (PEP) (Weeks 20 to 26)
The Baseline Hb was defined as the average of the last 2 central laboratory Hb values taken on or prior to the first dose date. The average for the PEP was calculated as the average of all Hb measurements from the central laboratory within the three visit windows during Weeks 20 through 26, regardless of intercurrent events. Analysis was conducted using an analysis of covariance (ANCOVA) model with multiple imputation for missing data with randomization stratification factors and Baseline Hb as covariates. Change from Baseline was calculated as PEP value minus the Baseline value.
Baseline; Weeks 20 to 26
Secondary Outcomes (1)
Change From Baseline in Hb to the Average Over the Secondary Evaluation Period (SEP) (Weeks 46 to 52)
Baseline; Weeks 46 to 52
Study Arms (3)
Vadadustat once daily (QD)
EXPERIMENTALVadadustat three times weekly (TIW)
EXPERIMENTALDarbepoetin alfa
ACTIVE COMPARATORInterventions
Eligibility Criteria
You may qualify if:
- Receiving chronic, outpatient three times weekly (TIW) in-center hemodialysis for end-stage renal disease for at least 12 weeks prior to Screening
- Hemodialysis adequacy as indicated by single-pool Kt/Vurea ≥ 1.2 using the most recent historical measurement within 8 weeks prior to or during Screening
- Use of any approved erythropoiesis-stimulating agents (ESAs) for at least the 8 weeks prior to Screening Visit 2
- Two hemoglobin (Hb) values, at least 4 days apart, measured by the central laboratory during Screening within the following prespecified ranges:
- Hb values between 8.0 and 11.0 grams per deciliter (g/dL) (inclusive) in the United States;
- Hb values between 9.0 and 12.0 g/dL (inclusive) in Europe
- Serum ferritin ≥ 100 nanograms per milliliter (ng/mL) and transferrin saturation (TSAT) ≥ 20% during Screening
- Folate and vitamin B12 measurements ≥ lower limit of normal during Screening
You may not qualify if:
- Anemia due to a cause other than chronic kidney disease (e.g., sickle cell disease, myelodysplastic syndromes, bone marrow fibrosis, hematologic malignancy, myeloma, hemolytic anemia, thalassemia, or pure red cell aplasia)
- Participants meeting cut-off of the following equivalent mean weekly doses calculated over 8 weeks prior to Screening Visit 2
- Methoxy polyethylene glycol-epoetin beta \> 50 micrograms (µg)/week;
- Darbepoetin alfa \> 100 µg/week;
- Epoetin analogues \> 23000 International Units (IU)/week
- Active bleeding or recent blood loss within 8 weeks prior to randomization
- Red blood cell transfusion within 8 weeks prior to randomization
- Current uncontrolled hypertension.
- Acute coronary syndrome (hospitalization for unstable angina or myocardial infarction), surgical or percutaneous intervention for coronary, cerebrovascular or peripheral artery disease (aortic or lower extremity), surgical or percutaneous valvular replacement or repair, sustained ventricular tachycardia, hospitalization for heart failure (HF) or New York Heart Association Class IV HF, or stroke within 12 weeks prior to or during Screening.
- Known hypersensitivity to vadadustat, darbepoetin alfa, or any of their excipients
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (59)
Research Site
Chula Vista, California, 91910, United States
Research Site
Granada Hills, California, 91344, United States
Research Site
Los Angeles, California, 90022, United States
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Lynwood, California, 90262, United States
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Northridge, California, 91324, United States
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San Dimas, California, 91773, United States
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Whittier, California, 90603, United States
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Denver, Colorado, 80230, United States
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Middlebury, Connecticut, 06762, United States
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Coral Gables, Florida, 33134, United States
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Tampa, Florida, 33614, United States
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Winter Park, Florida, 32789, United States
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Pontiac, Michigan, 48341, United States
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Roseville, Michigan, 48066, United States
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Minneapolis, Minnesota, 55404, United States
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Brookhaven, Mississippi, 39601, United States
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Tupelo, Mississippi, 38801, United States
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Kansas City, Missouri, 64111, United States
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St Louis, Missouri, 63136, United States
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Las Vegas, Nevada, 89128, United States
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Albuquerque, New Mexico, 87109, United States
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Durham, North Carolina, 27704, United States
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Kinston, North Carolina, 28504, United States
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New Bern, North Carolina, 28562, United States
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Bethlehem, Pennsylvania, 18017, United States
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Orangeburg, South Carolina, 29118, United States
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Chattanooga, Tennessee, 37404, United States
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Knoxville, Tennessee, 37920, United States
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Knoxville, Tennessee, 37923, United States
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Austin, Texas, 78751, United States
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Austin, Texas, 78758, United States
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El Paso, Texas, 79902, United States
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Houston, Texas, 77004, United States
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Houston, Texas, 77099, United States
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McAllen, Texas, 78503, United States
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San Antonio, Texas, 78204, United States
Research Site
San Antonio, Texas, 78212, United States
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San Antonio, Texas, 78229, United States
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Hampton, Virginia, 23666, United States
Research Site
Mariánské Lázně, Czechia
Research Site
Nový Jičín, Czechia
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Pilsen, Czechia
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Prague, Czechia
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Příbram, Czechia
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Slaný, Czechia
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Baja, Hungary
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Debrecen, Hungary
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Kaposvár, Hungary
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Kecskemét, Hungary
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Pécs, Hungary
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Pavia, Italy
Research Site
Vicenza, Italy
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Biała Podlaska, Poland
Research Site
Brodnica, Poland
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Lodz, Poland
Research Site
Pszczyna, Poland
Research Site
Sochaczew, Poland
Research Site #2
Barcelona, Spain
Research Site
Valencia, Spain
Related Publications (2)
Kooienga L, Burke S, Kathresal A, Luo W, Yang Z, Zhang Z, Zwiech R, Hernandez GT. Safety and Efficacy of Vadadustat Once Daily and Three Times Weekly in Patients With Dialysis-Dependent CKD With Anemia. Kidney360. 2024 Nov 1;5(11):1652-1661. doi: 10.34067/KID.0000000567. Epub 2024 Sep 4.
PMID: 39231617DERIVEDNatale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013751. doi: 10.1002/14651858.CD013751.pub2.
PMID: 36005278DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Per the protocol, data was collected by the arm to which participants were randomized and not by dose received in vadadustat QD or vadadustat TIW arms.
Results Point of Contact
- Title
- Akebia Therapeutics, Inc.
- Organization
- Akebia Therapeutics, Inc.
Study Officials
- STUDY DIRECTOR
Chief Medical Officer
Akebia Therapeutics Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Masking Details
- This is an open-label, Sponsor-blind study.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 16, 2020
First Posted
March 18, 2020
Study Start
May 27, 2020
Primary Completion
November 26, 2021
Study Completion
June 22, 2022
Last Updated
May 22, 2025
Results First Posted
May 22, 2025
Record last verified: 2025-05
Data Sharing
- IPD Sharing
- Will not share